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1.
Polymers (Basel) ; 16(2)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38276705

RESUMO

Polyimide (PI) composite films with enhanced mechanical properties were prepared by incorporating modified fumed silica (FS) particles while preserving their optical and thermal characteristics. The PI matrix was synthesized using a fluorinated diamine, a fluorinated dianhydride, and a rigid biphenyl dianhydride via chemical imidization. Commercially available FS particles, including unmodified FS particles (0-FS) and particles modified with dimethyl (2-FS), trimethyl (3-FS), octyl (8-FS), octamethylcyclotetrasiloxane (D4-FS), and polydimethylsiloxane (PDMS-FS) were used. Scanning electron microscope images and nitrogen adsorption-desorption isotherms revealed well-defined porous structures in the FS particles. The water contact angles on the composite films increased compared to those of the pristine PI films, indicating improved water resistance. The PI/0-FS films exhibited a typical trade-off relationship between tensile modulus and elongation at break, as observed in conventional composites. Owing to the poor compatibility and agglomeration of the PDMS-FS particles, the PI/PDMS-FS composite films exhibited poor mechanical performance and diminished optical characteristics. Although the longer-chained FS particles (8- and D4-FS) improved the tensile modulus of the PI film by up to 12%, a reduction of more than 20% in toughness was observed. The PI composite films containing the methylated FS particles (2- and 3-FS) outperformed 8- and D4-FS in terms of mechanical properties, with PI/3-FS films showing an over 10% increased tensile modulus (from 4.07 to 4.42 GPa) and 15% improved toughness (from 6.97 to 8.04 MJ/m3) at 7 wt. % silica loading. Except for the PI/PDMS-FS composites, all composite film samples exhibited more than 86% transmittance at 550 nm. Regarding thermal properties, the glass transition temperature (Tg) and thermal stability remained stable for most composite films. In addition, PI/3-FS films demonstrated enhanced dimensional stability with lower coefficients of thermal expansion (from 47.3 to 34.5 ppm/°C). Overall, this study highlights the potential of incorporating specific modified FS particles to tailor the mechanical, optical, and thermal properties of PI composite films.

2.
Polymers (Basel) ; 15(22)2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-38006132

RESUMO

Self-healing polymeric materials, engineered to autonomously self-restore damages from external stimuli, are at the forefront of sustainable materials research. Their ability to maintain product quality and functionality and prolong product life plays a crucial role in mitigating the environmental burden of plastic waste. Historically, initial research on the development of self-healing materials has focused on extrinsic self-healing systems characterized by the integration of embedded healing agents. These studies have primarily focused on optimizing the release of healing agents and ensuring rapid self-healing capabilities. In contrast, recent advancements have shifted the focus towards intrinsic self-healing systems that utilize their inherent reactivity and interactions within the matrix. These systems offer the advantage of repeated self-healing over the same damaged zone, which is attributed to reversible chemical reactions and supramolecular interactions. This review offers a comprehensive perspective on extrinsic and intrinsic self-healing approaches and elucidates their unique properties and characteristics. Furthermore, various self-healing mechanisms are surveyed, and insights from cutting-edge studies are integrated.

3.
Polymers (Basel) ; 15(23)2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38231957

RESUMO

In this study, we prepare highly self-healable polymeric coating materials using charge transfer complex (CTC) interactions. The resulting coating materials demonstrate outstanding thermal stability (1 wt% loss thermal decomposition temperature at 420 °C), rapid self-healing kinetics (in 5 min), and high self-healing efficiency (over 99%), which is facilitated by CTC-induced multiple interactions between the polymeric chains. In addition, these materials exhibit excellent optical properties, including transmittance over 91% and yellow index (YI) below 2, and show enhanced weatherability with a ΔYI value below 0.5 after exposure to UV light for 72 h. Furthermore, the self-healable coating materials developed in this study show outstanding mechanical properties by overcoming the limitations of conventional self-healing materials.

4.
Polymers (Basel) ; 14(23)2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36501576

RESUMO

Polymeric coating materials (PCMs) are promising candidates for developing next-generation flexible displays. However, PCMs are frequently subjected to external stimuli, making them highly susceptible to repeated damage. Therefore, in this study, a highly self-healing PCM based on a charge transfer complex (CTC) was developed, and its thermal, self-healing, and mechanical properties were examined. The self-healing material demonstrated improved thermal stability, fast self-healing kinetics (1 min), and a high self-healing efficiency (98.1%) via CTC-induced multiple interactions between the polymeric chains. In addition, it eliminated the trade-off between the mechanical strength and self-healing capability that is experienced by typical self-healing materials. The developed PCM achieved excellent self-healing and superior bulk (in-plane) and surface (out-of-plane) mechanical strengths compared to those of conventional engineering plastics such as polyether ether ketone (PEEK), polysulfone (PSU), and polyethersulfone (PES). These remarkable properties are attributed to the unique intermolecular structure resulting from strong CTC interactions. A mechanism for the improved self-healing and mechanical properties was also proposed by comparing the CTC-based self-healing PCMs with a non-CTC-based PCM.

5.
Polymers (Basel) ; 14(2)2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35054736

RESUMO

Superhydrophobic Al surfaces with excellent durability and anti-icing properties were fabricated by coating dual-scale rough Al substrates with fluorinated polysilazane (FPSZ). Flat Al plates were etched using an acidic solution, followed by immersion in boiling water to generate hierarchical micro-nano structures on their surfaces. The FPSZ coatings were synthesized by grafting 1H,1H,2H,2H-perfluorodecyltrimethoxysilane (FAS-17), a fluoroalkyl silane), onto methylpolysilazane, an organopolysilazane (OPSZ) backbone. The high water contact angle (175°) and low sliding angle (1.6°) of the FPSZ-coated sample with an FAS-17 content of 17.3 wt% promoted the efficient removal of a frozen ice column with a low ice adhesion strength of 78 kPa at -20.0 °C (70% relative humidity), which was 4.3 times smaller than that of an OPSZ-coated surface. The FPSZ-coated Al surface suppressed ice nucleation, leading to a decrease in ice nucleation temperature from -19.5 to -21.9 °C and a delay in freezing time from 334 to 4914 s at -19.0 °C compared with the OPSZ-coated Al surface. Moreover, after 40 icing-melting cycles the freezing temperature of a water droplet on the FPSZ-coated Al surface remained unchanged, whereas that on the FAS-17-coated Al surface increased from -22.3 to -20.7 °C. Therefore, the durability of the polymeric FPSZ coating was superior to that of the FAS-17 monolayer coating.

6.
Int Orthop ; 46(3): 563-571, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35098350

RESUMO

PURPOSE: Direct comparative results of patients with early stiffness after arthroscopic rotator cuff repair (ARCR) with and without steroid injection are still unclear. This study aimed to evaluate the clinical and structural effect of intra-articular steroid injection for early stiffness after ARCR. METHODS: From 2011 and 2016, a total of 417 patients who underwent ARCR for less than medium-sized tears with 35.8 ± 22.6 months follow-up were retrospectively analyzed. Patients with shoulder stiffness [forward flexion (FF) < 120˚] or pain at 2 months after ARCR were performed intra-articular steroid injection, and four groups were established [+ stiffness/ + injection (SI, 158 patients), + stiffness/-injection (SNI, 92 patients), -stiffness/ + injection (NSI, 33 patients), and -stiffness/-injection (NSNI, 134 patients)]. Shoulder range-of-motion (ROM) and functional score changes for over two years were analyzed, and six month tendon integrity were evaluated using magnetic resonance imaging. RESULTS: Comparing SI and SNI group, ROM (except internal rotation) and functional score changes did not differ during the early period (2-6 and 2-12 months). However, comparing whether steroid injected (SI/NSI) or not (SNI/NSNI), the formers showed significantly higher improvement of both ROM and functional scores during the early and late period (2-24 months). A six month tendon integrity was not different across four groups and whether steroid injected or not. CONCLUSIONS: Intra-articular steroid injections do not appear to have a short-term clinical improving effect by comparing patients with stiff shoulders after ARCR with and without steroid injections. However, intra-articular steroid injection at two months after ARCR did not affect the tendon integrity at post-operative six months.


Assuntos
Lesões do Manguito Rotador , Articulação do Ombro , Artroscopia/efeitos adversos , Artroscopia/métodos , Humanos , Injeções Intra-Articulares , Imageamento por Ressonância Magnética , Amplitude de Movimento Articular , Estudos Retrospectivos , Manguito Rotador/cirurgia , Lesões do Manguito Rotador/tratamento farmacológico , Lesões do Manguito Rotador/cirurgia , Articulação do Ombro/cirurgia , Resultado do Tratamento
7.
Medicine (Baltimore) ; 100(52): e28392, 2021 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-34967373

RESUMO

RATIONALE: Plastic endobiliary stents, after endoscopic retrograde cholangiopancreatography, can get spontaneously dislocated from the common bile duct and migrate intothe distal bowel. Most migrated biliary stents are removed with the passing of stool. However, migrated biliary stents can cause bowel perforation, albeit rarely, and surgical intervention may be required. Recently, we observed a colonic diverticular perforation caused by a migrated biliary stent, and we have reported this case with a review of the literature. PATIENTS CONCERNS: A 74-year-old man presented with severe right lower quadrant pain after biliary stent insertion 1month ago. DIAGNOSES: Abdominal computed tomography revealed perforation of the proximal ascending colon by the migrated biliary stent, combined with localized peritonitis. INTERVENTIONS: Emergency diagnostic laparoscopic examination revealed penetration of the proximal ascending colon by the plastic biliary stent, and right hemicolectomy was performed. OUTCOMES: On pathological examination, colonic diverticular perforation by the biliary stent was confirmed. The patient was discharged without any additional complications. LESSONS: Endoscopic retrograde cholangiopancreatography endoscopists must always be cautious of the possibility of stent migration in patients with biliary stents in situ. In cases of biliary stent dislocation from the common bile duct in asymptomatic patients, follow-up with serial, plain abdominal radiographs, and physical examination is needed until confirmation of spontaneous passage through stool. In symptomatic cases suggesting peritonitis, abdominal computed tomography scan confirmation is needed, and early intervention should be considered.


Assuntos
Doenças Biliares/terapia , Colangiopancreatografia Retrógrada Endoscópica , Divertículo do Colo , Perfuração Intestinal , Peritonite , Stents , Idoso , Doenças Biliares/complicações , Doenças Biliares/cirurgia , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/instrumentação , Divertículo do Colo/complicações , Humanos , Perfuração Intestinal/diagnóstico , Perfuração Intestinal/etiologia , Masculino , Peritonite/diagnóstico , Peritonite/etiologia , Stents/efeitos adversos
8.
Indian J Orthop ; 55(Suppl 1): 167-175, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34113425

RESUMO

BACKGROUND: If osteomyelitis is confined to the proximal humerus, arthroscopic debridement with multiple punctures at the infected bone might be sufficient to eradicate the septic shoulder with bone involvement. MATERIALS AND METHODS: From 2005 to 2017, 15 patients received arthroscopic debridement with multiple punctures. We included patients with septic shoulder arthritis with proximal bone involvement and excluded patients with glenohumeral joint destruction or extension of bone involvement to the diaphysis of the humerus. We performed multiple punctures for drainage of proximal humerus after complete arthroscopic debridement of septic soft tissue. Infection laboratory studies and postoperative magnetic resonance image were evaluated. For clinical outcome measurements, range of motion, pain visual analog scale, functional visual analog scale, American shoulder elbow surgeon scores, constant scores, and simple shoulder test were evaluated. RESULTS: There were 11 males and 4 females with a mean age of 53 years (range 28-73 years). Mean follow-up was 32 months (range 12-115 months). There was no reinfection case. The postoperative C-reactive protein levels were normalized in all. The postoperative magnetic resonance image showed no bony involvement of the proximal humerus in all patients except one patient. The clinical scores and range of motion were significantly improved postoperatively. Six patients underwent secondary surgery for rotator cuff tear at a mean time period of 25 months (range 4-104 months) from the index period. CONCLUSION: Septic shoulder with proximal bone involvement can be successfully treated with arthroscopic debridement with multiple punctures. LEVEL OF EVIDENCE: Level IV, treatment study.

10.
Sci Rep ; 10(1): 17466, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060768

RESUMO

We evaluated the prognostic implications of the circulating tumor cell (CTC) count in non-metastatic, HER2-negative breast cancer patients who failed to achieve pathologic complete response (pCR) after neoadjuvant chemotherapy (NCT). A total of 173, non-metastatic breast cancer patients treated with NCT were prospectively enrolled. CTCs were obtained from blood drawn pre-NCT and post-NCT using a SMART BIOPSY SYSTEM isolation kit (Cytogen Inc., Seoul, Korea) with immunofluorescence staining. Excluding 26 HER2-positive patients, Relapse-free survival (RFS) and overall survival (OS) related to the CTC count and the association of the CTC count with the treatment response to given therapy were analyzed in 147 HER2-negative patients. Among 147 HER2-negative patients, 28 relapses (19.0%) and 13 deaths (8.8%, all breast cancer-specific) were observed during a median follow-up of 37.3 months. One hundred and seven patients (72.8%) were hormone receptor-positive, and 40 patients (27.2%) had triple-negative breast cancer (TNBC). One or more CTCs were identified in 88 of the 147 patients (59.9%) before NCT and 77 of the 134 patients (52.4%) after NCT. In the entire HER2-negative patient cohort, the initial nodal status was the most significant factor influencing RFS and OS. In TNBC, 11 patients (27.5%) achieved pCR and patients that failed to achieve pCR with ≥ 5 CTCs after NCT, showed worse RFS (HR, 10.66; 95% CI, 1.80-63.07; p = 0.009) and OS (HR, 14.00; 95% CI, 1.26-155.53; p = 0.032). The patients with residual tumor and a high number of the CTCs after NCT displayed the worse outcome. These findings could provide justification to launch a future, well designed trial with longer follow-up data to obtain regulatory approval for clinical use of the assay, especially for the ER-positive, HER2-negative breast cancer subset.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Células Neoplásicas Circulantes/patologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/sangue , Contagem de Células , Quimioterapia Adjuvante , Intervalo Livre de Doença , Receptor alfa de Estrogênio/metabolismo , Feminino , Seguimentos , Humanos , Células MCF-7 , Microscopia de Fluorescência , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia/sangue , Neoplasia Residual/sangue , Neoplasia Residual/tratamento farmacológico , Prognóstico , Receptor ErbB-2/metabolismo , Recidiva , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/sangue
11.
Polymers (Basel) ; 12(4)2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32326281

RESUMO

A functional polyurethane based on the heterocyclic group was synthesized and its self-healing and mechanical properties were examined. To synthesize a heterocyclic polyurethane, a polyol and a heterocyclic compound with di-hydroxyl groups at both ends were blended and the blended solution was reacted with a crosslinker containing multiple isocyanate groups. The heterocyclic polyurethane demonstrates better self-healing efficiency than the conventional polyurethane with no heterocyclic groups. Furthermore, unlike the conventional self-healing materials, the heterocyclic polyurethane examined in this study shows an outstanding recovery of the mechanical properties after the self-healing process. These results are attributed to the unique supramolecular network resulting from the strong hydrogen bonding interaction between the urethane group and the heterocyclic group in the heterocyclic polyurethane matrix.

12.
Aesthetic Plast Surg ; 43(4): 1095-1101, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30989276

RESUMO

BACKGROUND: The development of fillers for wrinkle prevention is growing to meet rising demands to reduce the aging of skin. OBJECTIVE: In this experiment, we confirmed the effects of human collagen and hyaluronic acid filler biodegradation for wrinkle reduction using a photo-aging mouse model. MATERIALS AND METHODS: A total of 10 hairless mice (SKH1-Hrhr) were randomly divided into two groups and injected with hyaluronic acid and human-derived collagen filler. At 0, 2, 4, 8, and 12 weeks, PRIMOSlite®, folliscope, and MRI were used to evaluate the biodegradability of the fillers after the injections. We also studied the photo-aging mouse model for skin roughness and histological evaluation and confirmed that the filler injection had excellent anti-wrinkle effects. RESULTS: Human-derived collagen fillers had excellent biodegradability compared to that of hyaluronic acid fillers. The skin surface roughness in the photo-aging mouse models was significantly reduced after injections of human-derived collagen filler. CONCLUSION: Our results showed that the human-derived collagen filler had excellent biodegradability and effectively reduced wrinkle formation in a photo-aging mouse model. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Assuntos
Implantes Absorvíveis , Colágeno/farmacologia , Preenchedores Dérmicos/farmacologia , Ácido Hialurônico/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Análise de Variância , Animais , Biópsia por Agulha , Modelos Animais de Doenças , Feminino , Humanos , Imuno-Histoquímica , Injeções Intradérmicas , Camundongos , Camundongos Pelados , Distribuição Aleatória
13.
J Orthop Surg (Hong Kong) ; 27(1): 2309499018821771, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30798725

RESUMO

PURPOSE: The objective of the study is to determine clinical and radiological outcomes of arthroscopic repair for delaminated tears versus non-delaminated tears. METHODS: Consecutive 138 patients with full-thickness rotator cuff tear were retrospectively enrolled. They were divided into two groups based on the presence of delamination. All delaminated tears were repaired by en bloc technique (suturing both layers by single stitch). Delaminated tears were categorized into two types: (1) posterior type, delamination involving mainly infraspinatus and (2) complete type, delamination involving both supraspinatus and infraspinatus. Clinical assessments were done using pain visual analog scale (PVAS), functional VAS, American Shoulder Elbow Surgeons score, the Constant score, and range of motion. Postoperative MRI was performed at 6 months after surgery to determine repair integrity. RESULTS: Of the 138 patients, 78 (56.5%) had delaminated tears, including 30 cases of posterior type and 48 cases of complete type. The retear rate was 6.7% (4/60) in the non-delamination group and 5.1% (4/78) in the delamination group, showing no significant difference between the two groups. There was no significant difference in Sugaya classification between the two groups. Clinical scores were improved significantly in both delamination and non-delamination groups postoperatively, showing no significant difference between the two groups. Delamination subgroup (posterior or complete type) showed no significant correlation with retear rate, Sugaya classification, or clinical outcome. CONCLUSIONS: Arthroscopic en bloc repair for delaminated rotator cuff tear showed no significant difference in clinical or radiological outcome from that for non-delaminated rotator cuff tear. The extent of delamination did not affect outcome either. Levels of Evidence: Level III, Retrospective comparative study.


Assuntos
Artroscopia/métodos , Amplitude de Movimento Articular/fisiologia , Lesões do Manguito Rotador/cirurgia , Articulação do Ombro/cirurgia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Radiografia , Estudos Retrospectivos , Lesões do Manguito Rotador/diagnóstico , Lesões do Manguito Rotador/fisiopatologia , Ruptura , Articulação do Ombro/fisiopatologia , Suturas , Resultado do Tratamento
14.
Sci Rep ; 7: 45557, 2017 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-28367990

RESUMO

Liver cancer stem cells (LCSCs) have attracted attention because they cause therapeutic resistance in hepatocellular carcinoma (HCC). Understanding the metabolism of LCSCs can be a key to developing therapeutic strategy, but metabolic characteristics have not yet been studied. Here, we systematically analyzed and compared the global metabolic phenotype between LCSCs and non-LCSCs using transcriptome and metabolome data. We also reconstructed genome-scale metabolic models (GEMs) for LCSC and non-LCSC to comparatively examine differences in their metabolism at genome-scale. We demonstrated that LCSCs exhibited an increased proliferation rate through enhancing glycolysis compared with non-LCSCs. We also confirmed that MYC, a central point of regulation in cancer metabolism, was significantly up-regulated in LCSCs compared with non-LCSCs. Moreover, LCSCs tend to have less active fatty acid oxidation. In this study, the metabolic characteristics of LCSCs were identified using integrative systems analysis, and these characteristics could be potential cures for the resistance of liver cancer cells to anticancer treatments.


Assuntos
Antígeno AC133/metabolismo , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Metaboloma , Células-Tronco Neoplásicas/metabolismo , Análise de Sistemas , Transcriptoma , Animais , Apoptose , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Movimento Celular , Proliferação de Células , Feminino , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células-Tronco Neoplásicas/patologia , Transdução de Sinais , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Oncol Rep ; 37(2): 813-822, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27959451

RESUMO

Hepatocellular carcinoma (HCC) is the fifth most common solid cancer and the third most common cause of cancer-related mortality. HCC develops via a multistep process associated with genetic aberrations that facilitate HCC invasion and migration and promote metastasis. A growing body of evidence indicates that cancer stem cells (CSCs) are responsible for tumorigenesis, cancer cell invasion and metastasis. Despite the extremely small proportion of cancer cells represented by this subpopulation of HCC cells, CSCs play a key role in cancer metastasis and poor prognosis. ELK3 (Net/SAP-2/Erp) is a transcription factor that is activated by the Ras/extracellular signal-regulated kinase (ERK) signaling pathway. It plays several important roles in various physiological processes, including cell migration, invasion, wound healing, angiogenesis and tumorigenesis. In the present study, we investigated the role of ELK3 in cancer cell invasion and metastasis in CD133+/CD44+ liver cancer stem cells (LCSCs). We isolated LCSCs expressing CD133 and CD44 from Huh7 HCC cells and evaluated their metastatic potential using invasion and migration assays. We found that CD133+/CD44+ cells had increased metastatic potential compared with non-CD133+/CD44+ cells. We also demonstrated that ELK3 expression was upregulated in CD133+/CD44+ cells and that this aberration enhanced cell migration and invasion. In addition, we identified the molecular mechanism by which ELK3 promotes cancer cell migration and invasion. We found that silencing of ELK3 expression in CD133+/CD44+ LCSCs attenuated their metastatic potential by modulating the expression of heat shock-induced factor-1α (HIF-1α). Collectively, the results of the present study demonstrated that ELK3 overexpression promoted metastasis in CD133+/CD44+ cells by regulating HIF-1α expression and that silencing of ELK3 expression attenuated the metastatic potential of CD133+/CD44+ LCSCs. In conclusion, modulation of ELK3 expression may represent a novel therapeutic strategy for preventing HCC metastasis and invasion.


Assuntos
Carcinoma Hepatocelular/patologia , Movimento Celular , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Hepáticas/patologia , Células-Tronco Neoplásicas/patologia , Proteínas Proto-Oncogênicas/metabolismo , Fatores de Transcrição/metabolismo , Antígeno AC133/genética , Antígeno AC133/metabolismo , Apoptose , Western Blotting , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Proliferação de Células , Humanos , Receptores de Hialuronatos/genética , Receptores de Hialuronatos/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Invasividade Neoplásica , Células-Tronco Neoplásicas/metabolismo , Neovascularização Patológica , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-ets , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Fatores de Transcrição/genética , Células Tumorais Cultivadas
16.
Gut Liver ; 11(1): 102-111, 2017 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-27538444

RESUMO

BACKGROUND/AIMS: The role of Elk-3 in the epithelial-mesenchymal transition (EMT) during liver fibrogenesis remains unclear. Here, we determined the expression of Elk-3 in in vitro and in vivo models and in human liver fibrotic tissues. We also investigated the molecular relationships among Elk-3, early growth response-1 (Egr-1), and the mitogen activated protein kinases (MAPK) pathway during EMT in hepatocytes. METHODS: We established an in vitro EMT model in which normal mouse hepatocyte cell lines were treated with transforming growth factor (TGF)-ß1 and a CCl4-induced liver fibrosis model. Characteristics of EMT were determined by evaluating the expression levels of related markers. The expression of Elk-3 and its target Egr-1 were analyzed using Western blotting. Gene silencing of Elk-3 was performed using an siRNA knockdown system. RESULTS: The expression levels of mesenchymal markers were increased during TGF-ß1-induced EMT of hepatocytes. The expression levels of Elk-3 and Egr-1 were significantly (p<0.05) increased during the EMT of hepatocytes, in CCl4-induced mouse liver fibrotic tissues, and in human liver cirrhotic tissues. Silencing of Elk-3 and inhibition of the Ras-Elk-3 pathway with an inhibitor suppressed the expression of EMT-related markers. Moreover, Elk-3 expression was regulated by p38 MAPK phosphorylation during EMT. CONCLUSIONS: Elk-3 contributes to the progression of liver fibrosis by modulating the EMT via the regulation of Egr-1 under MAPK signaling.


Assuntos
Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Transição Epitelial-Mesenquimal/genética , Hepatócitos/metabolismo , Cirrose Hepática/genética , Proteínas Proto-Oncogênicas c-ets/genética , Actinas/metabolismo , Animais , Antígenos CD , Western Blotting , Caderinas/metabolismo , Tetracloreto de Carbono/toxicidade , Proteínas Cdh1/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Hepatócitos/efeitos dos fármacos , Humanos , Cirrose Hepática/metabolismo , Camundongos , Proteínas Quinases Ativadas por Mitógeno , Piperazinas/farmacologia , Proteínas Proto-Oncogênicas c-ets/metabolismo , Pirazóis/farmacologia , RNA Interferente Pequeno , Transdução de Sinais , Fator de Crescimento Transformador beta1/toxicidade , Vimentina/metabolismo
17.
J Cell Biochem ; 118(8): 2026-2036, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-27791279

RESUMO

The epithelial-mesenchymal transition (EMT) is involved in many different types of cellular behavior, including liver fibrosis. In this report, we studied a novel function of RAR-related orphan receptor gamma (ROR-γ) in hepatocyte EMT during liver fibrosis. To induce EMT in vitro, primary hepatocytes and FL83B cells were treated with TGF-ß1. Expression of ROR-γ was analyzed by Western blot in the fibrotic mouse livers and human livers with cirrhosis. To verify the role of ROR-γ in hepatocyte EMT, we silenced ROR-γ in FL83B cells using a lentiviral short hairpin RNA (shRNA) vector. The therapeutic effect of ROR-γ silencing was investigated in a mouse model of TAA-induced fibrosis by hydrodynamic injection of plasmids. ROR-γ expression was elevated in hepatocyte cells treated with TGF-ß1, and ROR-γ protein levels were elevated in the fibrotic mouse livers and human livers with cirrhosis. Knockdown of ROR-γ resulted in the attenuation of TGF-ß1-induced EMT in hepatocytes. Strikingly, ROR-γ bound to ROR-specific DNA response elements (ROREs) in the promoter region of TGF-ß type I receptor (Tgfbr1) and Smad2, resulting in the downregulation of Tgfbr1 and Smad2 after silencing of ROR-γ. Therapeutic delivery of shRNA against ROR-γ attenuated hepatocyte EMT and ameliorated liver fibrosis in a mouse model of TAA-induced liver fibrosis. Overall, our results suggest that ROR-γ regulates TGF-ß-induced EMT in hepatocytes during liver fibrosis. We suggest that ROR-γ may become a potential therapeutic target in treating liver fibrosis. J. Cell. Biochem. 118: 2026-2036, 2017. © 2016 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals Inc.


Assuntos
Transição Epitelial-Mesenquimal/genética , Hepatócitos/metabolismo , Cirrose Hepática/genética , Fígado/metabolismo , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Caderinas/genética , Caderinas/metabolismo , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Regulação da Expressão Gênica , Hepatócitos/efeitos dos fármacos , Hepatócitos/patologia , Humanos , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/metabolismo , Cirrose Hepática/terapia , Camundongos , Camundongos Endogâmicos BALB C , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/antagonistas & inibidores , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Cultura Primária de Células , Regiões Promotoras Genéticas , Ligação Proteica , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I , Receptores de Fatores de Crescimento Transformadores beta/genética , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Transdução de Sinais , Proteína Smad2/genética , Proteína Smad2/metabolismo , Tioacetamida , Fator de Crescimento Transformador beta1/farmacologia
18.
Toxicol In Vitro ; 36: 210-215, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27511800

RESUMO

Our 3-dimensional testis co-culture system (3D-TCS) represents a promising model of male reproductive toxicity which captures sensitive processes of male reproductive development and contains the main testes cell types (germ, Leydig and Sertoli cells). Macrophages are another cell type important for testicular function and help to modulate immuno-endocrine processes during testes development. Chemicals such as phthalate esters (PE's) affect macrophage function and testosterone production in the testes in vivo. The aim of this study was to determine whether macrophages were present in the 3D-TCS and investigate responses in our model that may be related to immuno-endocrine functions. We observed consistent expression of the resident macrophage marker ED2 as well as increases in inflammatory cytokines produced by macrophages and testes cells (IL-6, TNF-α and KC/GRO) after exposure to toxic PE's. Pathway analysis of gene expression changes after exposure to PE's showed that IL-6 and TNF-α signaling pathways were enriched after treatment with reproductively toxic, but not non-reproductively toxic phthalates. These results indicate that macrophages and inflammatory processes are captured in the 3D-TCS and that these processes are impacted by exposure to reproductive toxicants. These processes represent a major mode of action for in vivo testis toxicity for a variety of compounds and our novel in vitro model is able to capture toxicant perturbation of immune function.


Assuntos
Macrófagos/efeitos dos fármacos , Ácidos Ftálicos/toxicidade , Testículo/citologia , Animais , Técnicas de Cocultura , Citocinas/genética , Citocinas/metabolismo , Células Germinativas/efeitos dos fármacos , Células Germinativas/metabolismo , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Macrófagos/metabolismo , Masculino , Ratos Sprague-Dawley , Reprodução , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/metabolismo , Transcriptoma/efeitos dos fármacos
19.
Asia Pac J Clin Nutr ; 25(2): 308-15, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27222414

RESUMO

BACKGROUND AND OBJECTIVES: Drinking is a risk factor of osteoporosis, but controversy surrounds the relationship between alcohol consumption and bone mineral density (BMD). We performed an analysis of the association between alcohol consumption and BMD. METHODS AND STUDY DESIGN: A cross-sectional study was performed including 2421 men, aged 40-93 years, who participated in the fourth Korea National Health and Nutrition Examination Survey in 2008-2009. Alcohol intake was determined by self-administered questionnaires, and BMD was measured by dual energy x-ray absorptiometry. ANOVA was used to determine the relationship between alcohol intake and BMD, and ANCOVA was performed after adjusting for age, body mass index, education, household income, smoking status, calcium intake, physical activity, and serum 25-hydroxyvitamin D levels. RESULTS: BMD increased significantly in the lumbar spine, total femur, and femoral neck with increased alcohol intake (p for trend=0.028, <0.001, <0.001, respectively). However, after adjusting for age, the relation was no longer statistically significant in any of 3 bone sites (lumbar, p for trend=0.606; total femur, p for trend=0.342; femoral neck, p for trend=0.549). Additionally, after adjusting for all other confounders, no significant relationships were reported in the 3 bone sites (lumbar, p for trend=0.451; total femur, p for trend=0.150; femoral neck, p for trend=0.343). In the stratified analysis, there were no significant correlations according to age, smoking status, physical activity or obesity. CONCLUSIONS: After adjusting for age and other confounders, no significant relationship was found between alcohol intake and BMD.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Densidade Óssea , Inquéritos Nutricionais/estatística & dados numéricos , Absorciometria de Fóton , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Comorbidade , Estudos Transversais , Fêmur/diagnóstico por imagem , Colo do Fêmur/diagnóstico por imagem , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Fatores de Risco , Inquéritos e Questionários
20.
Oncotarget ; 7(17): 23482-97, 2016 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-26993601

RESUMO

We investigated the biological role of CD133-expressing liver cancer stem cells (CSCs) enriched after irradiation of Huh7 cells in cell invasion and migration. We also explored whether a disintegrin and metalloproteinase-17 (ADAM17) influences the metastatic potential of CSC-enriched hepatocellular carcinoma (HCC) cells after irradiation. A CD133-expressing Huh7 cell subpopulation showed greater resistance to sublethal irradiation and specifically enhanced cell invasion and migration capabilities. We also demonstrated that the radiation-induced MMP-2 and MMP-9 enzyme activities as well as the secretion of vascular endothelial growth factor were increased more predominantly in Huh7CD133+ cell subpopulations than Huh7CD133- cell subpopulations. Furthermore, we showed that silencing ADAM17 significantly inhibited the migration and invasiveness of enriched Huh7CD133+ cells after irradiation; moreover, Notch signaling was significantly reduced in irradiated CD133-expressing liver CSCs following stable knockdown of the ADAM17 gene. In conclusion, our findings indicate that CD133-expressing liver CSCs have considerable metastatic capabilities after irradiation of HCC cells, and their metastatic capabilities might be maintained by ADAM17. Therefore, suppression of ADAM17 shows promise for improving the efficiency of current radiotherapies and reducing the metastatic potential of liver CSCs during HCC treatment.


Assuntos
Antígeno AC133/metabolismo , Proteína ADAM17/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/secundário , Raios gama , Neoplasias Hepáticas/patologia , Células-Tronco Neoplásicas/patologia , Animais , Apoptose/efeitos da radiação , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/radioterapia , Adesão Celular/efeitos da radiação , Movimento Celular/efeitos da radiação , Proliferação de Células/efeitos da radiação , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/radioterapia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/efeitos da radiação , Transdução de Sinais , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
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